Alterations in pulmonary function in guinea pigs, especially flow resistance and dynamic (in some instances also static) compliance, are used to assess quantitatively the response to respiratory irritants. Exposure to ozone for 1 hr at concentrations of 0.8 ppm causes an increased response to a challenge with histamine (0.125 mg/cubic m, s.c. or as an aerosol) given two hours post-exposure. We find that this increased bronchial sensitivity to histamine is abolished by vagotomy but not be atropine or vitamine E. Ozone exposure decreases slightly the acetycholine esterase level of lung and diaphragm. Pre-exposure to ozone also increases the response to serotonin. Our current plans include the pre-treatment of animals with indomethicin, a general prostoglandin synthesis inhibitor, to test the involvement of prostoglandins in the observed bronchial hypersensitivity. Specific prostoglandin inhibitors will be used if preliminary results with indomethicin are positive. The effect of ozone pre-exposure will be examined on the response to sulfuric acid aerosol and to an organophosphorous insecticide. Both these agents produce branchoconstriction and an increase in this response by ozone exposure could have practical implications in areas of high oxidant pollution.